ACE inhibitors and angiotensin receptor blockers (ARB) in heart failure

• the ELITE trial has examined the role of angiotensin II receptor inhibitors in the management of heart failure. This revealed that losartan and enalapril have similar effects on exercise capacity and haemodynamics (1). However the size of the study was not large enough to reliably assess effects on survival
  
  
• in the CHARM study
  • in this study candesartan significantly reduces all-cause mortality, cardiovascular death, and heart failure hospitalizations in patients with chronic heart failure and left ventricular ejection fraction < or =40% when added to standard therapies including ACE inhibitors, beta-blockers, and an aldosterone antagonist

NICE recommend that (3):

• consider an ARB licensed for heart failure as an alternative to an ACE inhibitor for patients with heart failure due to left ventricular systolic dysfunction who have intolerable side effects with ACE inhibitors
  
  
• measure serum sodium and potassium, and assess renal function, before and after starting an ARB and after each dose increment
  
  
• measure blood pressure after each dose increment of an ARB - follow the recommendations on measuring blood pressure, including measurement in people with symptoms of postural hypotension
  
  
• once the target or maximum tolerated dose of an ARB is reached, monitor treatment monthly for 3 months and then at least every 6 months, and at any time the person becomes acutely unwell

Notes:

• a meta-analysis concluded that, in patients with chronic heart failure or high risk acute myocardial infarction, angiotensin receptor blockers do not differ from angiotensin converting enzyme inhibitors for all cause mortality or hospital admission for heart failure (4)
• ARBs in heart failure with preserved left ventricular ejecation fraction
  • study evidence revealed that irbesartan did not improve the outcomes of patients with heart failure and a preserved left ventricular ejection fraction (ejection fraction >= 45%)

Reference:

• (1) Pitt, B. et al. Randomised trial of losartan versus captopril in patients over 65 with heart failure (Evaluation of Losartan in the Elderly Study, ELITE). Lancet 1997; 349: 747-752.
• (2) Young JB et al. Mortality and morbidity reduction with Candesartan in patients with chronic heart failure and left ventricular systolic dysfunction: results of the CHARM low-left ventricular ejection fraction trials. Circulation. 2004 Oct 26;110(17):2618-26. Epub 2004 Oct 18
• (3) NICE (September 2018). Chronic heart failure
• (4) Lee VC et al. Meta-analysis: angiotensin-receptor blockers in chronic heart failure and high-risk myocardial infarction. Ann Intern Med 2004;141:693-704
• (5) Massie BM et al. Irbesartan in patients with heart failure and preserved ejection fraction.N Engl J Med. 2008 Dec 4;359(23):2456-67.